Cell regeneration brings hope for diabetics

Some cells in the adult pancreas can, in times of extreme stress, produce new insulin-secreting cells, researchers have found.

The findings, based on work performed in mice, open up a new approach to replacing insulin-secreting cells in patients with
diabetes. They also address a raging controversy within the diabetes research community over whether such cells even exist.

“It’s a big discovery,” says Emmanuel Baetge, chief scientific officer of Novocell, a stem cell company based in San Diego,
California who was not involved with the work. “I think this will heat up the whole field.”

The blood and heart are known to be supplied with new cells by adult stem cells capable of generating a fresh stock. If such
regenerative stem cells existed in the pancreas, they could perhaps be harnessed to restock the supply of pancreatic ß cells,
which in turn produce insulin. This could form the basis of treatment for patients with type 1 diabetes who have fewer ß cells.

At least, that was the hope. Researchers tried and failed repeatedly to find such cells in the pancreas. “Most people, including
me, concluded that the pancreas was very different,” says Douglas Melton, a Harvard University stem-cell researcher in Cambridge,
Massachusetts.

Limited options

Without regenerative stem cells, there seemed to be only two ways to generate new ß cells in diabetics: encourage whatever
few ß cells the patient still has to divide; or programme embryonic stem cells to produce the needed cell type and inject
those into the patient.

Unfortunately, ß cells are difficult to isolate and grow very slowly in culture, making it difficult to boost their numbers.
Embryonic stem cells are easier to grow, but difficult to programme. “There, the challenge is how to tell them what to do,”
says Melton. Researchers from Baetge’s group have come close: embryonic stem cells have been coaxed into forming ß cells1, but these cells were only marginally sensitive to glucose so wouldn't be able to regulate insulin production in diabetics.

Harry Heimberg, a researcher at the Diabetes Research Center at Vrije University in Brussels, Belgium, and his colleagues
instead continued the hunt for pancreatic stem cells.

A new hope

Researchers had previously looked for the specific stem cells by damaging the pancreas, watching new ß cells come into existence,
and then tracing them back to source. This showed that the new ß cells were emerging simply from the division of existing
ones.

Heimberg and his colleagues damaged mouse pancreases in a different way: by clamping the duct that drains digestive enzymes
from the pancreas. This causes inflammation and a doubling of ß cell numbers. “If you think of your head as the pancreas and
the neck as the duct, they grabbed the neck and choked it,” says Melton.

When the researchers investigated the new cells, they found a population expressing a protein normally found only in embryonic
pancreatic cells; a sign that stem cells may be involved. When the researchers checked, these cells could generate new ß cells
capable of responding to glucose. The results are reported this week in Cell2.

Sleeping beauties

The work shows that mice can replenish insulin-producing ß cells — at least when pushed. Technically, the cells may not meet
all the requirements to be classified as adult stem cells — to prove that, the researchers will need to go on to show that
the cells can also replenish themselves. But the cells may hold therapeutic promise regardless, says Baetge, who has been
working with embryonic stem cells to make ß cells.

“If you could design a strategy by which you could stimulate those cells not through injury, but some other mechanism, you
might be able to use them to treat diabetes,” Baetge says.

Now that the struggle to find such cells is over, researchers can begin to address these questions, says Heimberg. “They were
quite hard to find,” says Heimberg of the regenerative cells. “I sometimes call them sleeping beauties. They are hard to wake
up.”